Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel

@inproceedings{Liu2011SerendipitousAO,
  title={Serendipitous alkylation of a Plk1 ligand uncovers a new binding channel},
  author={Fa Liu and Jung-Eun Park and W. Qian and Dan Lim and Martin Gr{\"a}ber and Thorsten Berg and Michael B. Yaffe and Kyung S Lee and Terrence R. Burke},
  booktitle={Nature chemical biology},
  year={2011}
}
We obtained unanticipated synthetic byproducts from alkylation of the δ(1) nitrogen (N3) of the histidine imidazole ring of the polo-like kinase-1 (Plk1) polo-box domain (PBD)-binding peptide PLHSpT. For the highest-affinity byproduct, bearing a C(6)H(5)(CH(2))(8)- group, a Plk1 PBD cocrystal structure revealed a new binding channel that had previously been occluded. An N-terminal PEGylated version of this peptide containing a hydrolytically stable phosphothreonyl residue (pT) bound the Plk1… CONTINUE READING

Citations

Publications citing this paper.
SHOWING 1-10 OF 28 CITATIONS

Putting a bit into the polo-box domain of polo-like kinase 1

  • Journal of Analytical Science and Technology
  • 2015
VIEW 5 EXCERPTS
CITES BACKGROUND

References

Publications referenced by this paper.
SHOWING 1-10 OF 47 REFERENCES

Computational analysis of phosphopeptide binding to the polo-box domain of the mitotic kinase PLK1 using molecular dynamics simulation

DJ Huggins
  • PLoS Comput Biol
  • 2010

A Genome-wide RNAi screen identifies multiple synthetic lethal interactions with the ras oncogene

J Luo
  • 2009

A case study from the chemistry core of the Pittsburgh molecular library screening center: the polo-like kinase polo-box domain (Plk1-PBD)

P Wipf
  • Curr Top Med Chem
  • 2009